DESCRIPTION: (Adapted from the application) Caloric restriction produces reductions in sympathetic activity and blood pressure. The central aim of the project is to determine the mechanisms by which negative energy balance causes sympatho-inhibition and decreased blood pressure. The proposal will test the hypothesis that regulatory pathways involved in energy balance homeostasis are primarily responsible for sympathoinhibition and reductions in blood pressure during negative energy balance. Spontaneously hypertensive and aortic-coarctation-induced hypertensive rats, as well as normotensive controls, will be chronically instrumented for cardiovascular studies and tethered in metabolic cages for continuous assessment of BP and intravenous infusion of solutions during 48 hours of normal energy intake or food deprivation. To test the hypothesis that reductions in plasma insulin are primary signal requisite for fasting induced decreases in BP, euglycemic peripheral insulin infusions will be performed to maintain normal insulin levels during periods of food deprivation. In addition to insulin, it is now clear that leptin is an important signal in energy homeostasis. The potential contributions of leptin to cardiovascular actions of negative energy balance will be examined using both peripheral and central leptin infusions. Finally, hypothalamic administration of NPY receptor antagonists and antisense will be used to test the hypothesis that increases in hypothalamic NPY during negative energy balance contribute to reductions in blood pressure and sympathetic activity. The outcomes of these studies will produce important advancements in the understanding of the relationships between energy balance and blood pressure regulation.